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Cystic fibrosis (CF) is a success story of modern medicine, with advances in care transforming a disease previously associated with early childhood death into a chronic condition with a predicted median survival of nearly 50 years for patients born in this current decade.1 This has been achieved through a model of multidisciplinary care with the successive advent of supportive therapies that tackled the consequences of the condition, such as replacement pancreatic enzymes, inhaled antibiotics and agents to improve mucociliary clearance. The quest for treatments that address the underlying basic defect has been a hope for the CF community since the discovery of the CF gene, which codes for the dysfunctional channel protein, the CF transmembrane conductance regulator (CFTR), in 1989.2 The Cystic Fibrosis Foundation supported an ambitious pipeline to identify molecules that could allow correction of the dysfunctional CFTR protein, which began to bear the fruits of investment with the treatment of CF patients with Gly551Asp (G551D) mutation with ivacaftor.
The Gly551Asp mutation produces a CFTR protein that localises to the epithelial cell membrane but fails to open. Ivacaftor acts as a CFTR potentiator that increases channel opening probability and has demonstrated remarkable improvements in lung function, nutritional status, patient-reported outcome measures and biomarkers of CFTR function in clinical studies of patients with the Gly551Asp gene mutation.3 ,4 The initial promise of these significant clinical benefits seen in pre-licensing clinical studies has been fulfilled in subsequent postmarketing phase IV studies.5–7 In addition, published case reports and anecdotal comments from patients have exemplified the benefits of such therapy beyond the respiratory system in addressing the dysfunction that CF causes in other organs and systems.8–10
The unprecedented success of ivacaftor treatment for the Gly551Asp CF patient population has created immense excitement within the CF community with anticipation …